Endocannabinoids Could Modulate Various Mood Disorders

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If you experience constant ups and downs in your
mood...on-off, on-off to the extent that you struggle to find the emotional
balance to deal with circumstances of life, then you could be suffering from a
neuropsychiatric condition known as mood disorder.

Endocannabinoids Could Modulate Various Mood Disorders

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Mood disorders disturb the
rhythm of your body, the melody of your mind and the harmony of your soul, thus
affecting your quality of life to a great extent. It is estimated that nearly 17.5%
of the US population suffers from a mood disorder and as high as 30.7% of the
population is at a significant risk of developing one in their lifetime.

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Mental disorders and other depressive episodes have
become inherent in our society and have the highest rate of prevalence and
incidence of morbidity. Untreated cases could end up in suicides.

It is a known fact that the main cause of mood
disorders is an imbalance of chemicals in the brain which primarily affect your
mood. Irregularities in dopamine is known to lead to psychosis and schizophrenia whereas disruptions in
noradrenaline and serotonin could lead to bipolar disorder and depression.

Currently, a plethora of techniques such as
psychotherapy, cognitive behavioral therapy, electroconvulsive therapy are
utilized to help restore brain chemistry and treat psychiatric symptoms.
Anticonvulsant drugs, antipsychotic drugs,
antidepressants are used to treat various manic episodes, but they all carry the
risk of cognitive and somatic side effects which have to be closely monitored
by a qualified health practitioner.

Hence there is a need to explore alternative
neurochemical systems for treatment of mood disorders. Endogenous cannabinoid
system (ECS) is one such system.

There are two main cannabinoid receptor proteins CB1
and CB2. Research has shown increase in CB1 density in the brain, particularly
the dorsolateral prefrontal cortex of individuals who suffered from depression
or those who committed suicide. Thus an increase in the activity in the
dorsolateral prefrontal cortex could possibly promote pessimistic biases, which
includes negative emotional memories and negative mood disturbances in people
who are depressed. Hence a protective response would be the upregulation of
CB1-mediated endocannabinoid signaling in the dorsolateral prefrontal cortex
region.

The synthesis of endogenous cannabinoid ligands,
namely, N-arachidonoylethanolamide (AEA; anandamide) and
sn-2-arachidonoylglycerol (2-AG) are initiated by distinct signaling cascades,
mainly in response to demand from their arachidonate precursor in membrane
phospholipids.

In a study conducted in rats, it was seen that rats who
were put under chronic unpredictable or mild stress (CUS), which involved daily
administration of various stressors such as forced swim, cage rotations, social
isolation, deprivation from water etc., exhibited an increased secretion of corticosteroids and pro-inflammatory
chemo/cytokines, just as observed in depressed humans.

Chronic unpredictable stress reportedly also alters the
physiology of various neural structures including the amygdala, prefrontal
cortex, hippocampus, hypothalamus and ventral striatum, which brings about mood
disorders.

Researchers observed that low doses of drugs which
activate cannabinoid receptor protein-CB1 (agonists) exhibited antidepressant
and anxiolytic effects, while high doses exhibited strong anxiogenic effects.
In classic behavioral tests, scientists found that indirect enhancement of CB1-
mediated signaling also demonstrate antidepressant and anxiolytic effects, thus
exhibiting good potential for a new pharmacotherapy for mood disorders
including depression.

Thus, it was seen that augmenting CB1-mediated
endocannabinoid signaling in the brain is shown to modulate cognitive-affective
circuits and rescue both affective and somatic symptoms of depression in rat
models, making them a good candidate for treatment of mood disorders. However,
this research is only in the pre-clinical stage and more clinical trials are
required in the near future, especially in humans, to
bring about new pharmacotherapies for anxiety, depression and other affective
disorders.

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